Leucine-Rich Glioma Inactivated 3 Induces Neurite Outgrowth Through Akt and Focal Adhesion Kinase

被引:28
作者
Park, Woo-Jae [1 ]
Lim, Yun Young [2 ]
Kwon, Nyoun Soo [1 ]
Baek, Kwang Jin [1 ]
Kim, Dong-Seok [1 ]
Yun, Hye-Young [1 ]
机构
[1] Chung Ang Univ, Coll Med, Dept Biochem, Seoul 156756, South Korea
[2] Chung Ang Univ, Coll Med, Dept Dermatol, Seoul 156756, South Korea
关键词
LGI3; Neurite; Akt; FAK; Phosphorylation; Differentiation; LGI1; GENE; EPILEPSY; MUTATIONS; REPEAT; BRAIN; ASTROCYTES; PROTEINS; GROWTH; 10Q24; FAK;
D O I
10.1007/s11064-010-0136-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein that belongs to LGI/epitempin family. LGI3 is highly expressed in brain in a transcriptionally and developmentally regulated manner. Here we found that LGI3 induced neurite outgrowth in Neuro-2a cells and dorsal root ganglia explants. LGI3 treatment or overexpression increased neurite outgrowth and knockdown of LGI3 by siRNA had opposite effect. LGI3 treatment increased phosphorylation of Akt and a 125-kDa protein. Immunoprecipitation identified the 125-kDa protein as focal adhesion kinase (FAK). LGI3 overexpression increased phospho-Akt, phospho-FAK and FAK protein. Inhibition of Akt activation by PI3 kinase inhibitor attenuated LGI3-induced FAK phosphorylation and neurite outgrowth. Taken together, we propose that LGI3 is a neuritogenic factor whose signaling pathway involves Akt-mediated FAK activation.
引用
收藏
页码:789 / 796
页数:8
相关论文
共 24 条
[1]   Melanocortin receptors mediate alpha-MSH-induced stimulation of neurite outgrowth in Neuro 2A cells [J].
Adan, RAH ;
vanderKraan, M ;
Doornbos, RP ;
Bar, PR ;
Burbach, JPH .
MOLECULAR BRAIN RESEARCH, 1996, 36 (01) :37-44
[2]   The claw paw mutation reveals a role for Lgi4 in peripheral nerve development [J].
Bermingham, JR ;
Shearin, H ;
Pennington, J ;
O'Moore, J ;
Jaegle, M ;
Driegen, S ;
van Zon, A ;
Darbas, A ;
Özkaynak, E ;
Ryu, EJ ;
Milbrandt, J ;
Meijer, D .
NATURE NEUROSCIENCE, 2006, 9 (01) :76-84
[3]   The phosphoinositide 3-kinase pathway [J].
Cantley, LC .
SCIENCE, 2002, 296 (5573) :1655-1657
[4]   Cell adhesion and signalling by cadherins and Ig-CAMs in cancer [J].
Cavallaro, U ;
Christofori, G .
NATURE REVIEWS CANCER, 2004, 4 (02) :118-132
[5]   A novel gene, LGI1, from 10q24 is rearranged and downregulated in malignant brain tumors [J].
Chernova, OB ;
Somerville, RPT ;
Cowell, JK .
ONCOGENE, 1998, 17 (22) :2873-2881
[6]   LGI1 is mutated in familial temporal lobe epilepsy characterized by aphasic seizures [J].
Gu, WL ;
Brodtkorb, E ;
Steinlein, OK .
ANNALS OF NEUROLOGY, 2002, 52 (03) :364-367
[7]   The LGI1 gene involved in lateral temporal lobe epilepsy belongs to a new subfamily of leucine-rich repeat proteins [J].
Gu, WL ;
Wevers, A ;
Schröder, H ;
Grzeschik, KH ;
Derst, C ;
Brodtkorb, E ;
de Vos, R ;
Steinlein, OK .
FEBS LETTERS, 2002, 519 (1-3) :71-76
[8]   Regional distribution of the leucine-rich glioma inactivated (LGI), gene family transcripts in the adult mouse brain [J].
Herranz-Perez, Vicente ;
Eliseo Olucha-Bordonau, Francisco ;
Manuel Morante-Redolat, Jose ;
Perez-Tur, Jordi .
BRAIN RESEARCH, 2010, 1307 :177-194
[9]   Pyk2 and FAK regulate neurite outgrowth induced by growth factors and integrins [J].
Ivankovic-Dikic, I ;
Grönroos, E ;
Blaukat, A ;
Barth, BU ;
Dikic, I .
NATURE CELL BIOLOGY, 2000, 2 (09) :574-581
[10]   Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features [J].
Kalachikov, S ;
Evgrafov, O ;
Ross, B ;
Winawer, M ;
Barker-Cummings, C ;
Boneschi, FM ;
Choi, C ;
Morozov, P ;
Das, K ;
Teplitskaya, E ;
Yu, A ;
Cayanis, E ;
Penchaszadeh, G ;
Kottmann, AH ;
Pedley, TA ;
Hauser, WA ;
Ottman, R ;
Gilliam, TC .
NATURE GENETICS, 2002, 30 (03) :335-341